A river runs through it - ancient DNA data on the neolithic populations of the Great Hungarian Plain

This thesis was part of a multidisciplinary research project funded by the German Research Foundation (“Bevölkerungsgeschichte des Karpatenbeckens in der Jungsteinzeit und ihr Einfluss auf die Besiedlung Mitteleuropas”, grant no. Al 287/10-1) aimed at elucidating the population history of the Carpathian Basin during the Neolithic. The Carpathian Basin was an important waypoint on the spread of the Neolithic from southeastern to central Europe. On the Great Hungarian Plain (Alföld), the first farming communities appeared around 6000 cal BC. They belonged to the Körös culture, which derived from the Starčevo-Körös-Criş complex in the northern Balkans. Around 5600 cal BC the Alföld-Linearbandkeramik (ALBK), so called due to its stylistic similarities with the Transdanubian and central European LBK, emerged in the northwestern Alföld. Following a short “classical phase”, the ALBK split into several regional subgroups during its later stages, but did not expand beyond the Great Hungarian Plain. Marking the beginning of the late Neolithic period, the Tisza culture first appeared in the southern Alföld around 5000 cal BC and subsequently spread into the central and northern Alföld. Together with the Herpály and Csőszhalom groups it was an integral part of the late Neolithic cultural landscape of the Alföld. Up until now, the Neolithic cultural succession on the Alföld has been almost exclusively studied from an archaeological point of view, while very little is known about the population genetic processes during this time period. The aim of this thesis was to perform ancient DNA (aDNA) analyses on human samples from the Alföld Neolithic and analyse the resulting mitochondrial population data to address the following questions: is there population continuity between the Central European Mesolithic hunter-gatherer metapopulation and the first farming communities on the Alföld? Is there genetic continuity from the early to the late Neolithic? Are there genetic as well as cultural differences between the regional groups of the ALBK? Additionally, the relationships between the Alföld and the neighbouring Transdanubian Neolithic as well as other European early farming communities were evaluated to gain insights into the genetic affinities of the Alföld Neolithic in a larger geographic context. 320 individuals were analysed for this study; reproducible mitochondrial haplogroup information (HVS-I and/or SNP data) could be obtained from 242 Neolithic individuals. According to the analyses, population continuity between hunter-gatherers and the Neolithic cultures of the Alföld can be excluded at any stage of the Neolithic. In contrast, there is strong evidence for population continuity from the early to the late Neolithic. All cultural groups on the Alföld were heavily shaped by the genetic substrate introduced into the Carpathian Basin during the early Neolithic by the Körös and Starčevo cultures. Accordingly, genetic differentiation between regional groups of the ALBK is not very pronounced. The Alföld cultures are furthermore genetically highly similar to the Transdanubian Neolithic cultures, probably due to common ancestry. In the wider European context, the Alföld Neolithic cultures also highly similar to the central European LBK, while they differ markedly from contemporaneous populations of the Iberian Peninsula and the Ukraine. Thus, the Körös culture, the ALBK and the Tisza culture can be regarded as part of a “genetic continuum” that links the Neolithic Carpathian Basin to central Europe and likely has its roots in the Starčevo -Körös-Criş complex of the northern Balkans.

Mid-Holocene Climate and Culture Change in the South Central Ande

This chapter reviews the history of study and the current status of Mid-Holocene climatic and cultural change in the South Central Andes, which host a wide range of different habitats from Pacific coastal areas up to extremely harsh cold and dry environments of the high mountain plateau, the altiplano or the puna. Paleoenvironmental information reveals high amplitude and rapid changes in effective moisture during the Holocene period and, consequently, dramatically changing environmental conditions. Therefore, this area is suitable to study the response of hunting and gathering societies to environmental changes, because the smallest variations in the climatic conditions have large impacts on resources and the living space of humans. This chapter analyzes environmental and paleoclimatic information from lake sediments, ice cores, pollen profiles, and geomorphic processes and relates these with the cultural and geographic settlement patterns of human occupation in the different habitats in the area of southern Peru, southwest Bolivia, northwest Argentina, and north Chile and puts in perspective of the early and late Holocene to present a representative range of environmental and cultural changes. It has been found that the largest changes took place around 9000 cal yr BP when the humid early Holocene conditions were replaced by extremely arid but highly variable climatic conditions. These resulted in a marked decrease of human occupation, “ecological refuges,” increased mobility, and an orientation toward habitats with relatively stable resources (such as the coast, the puna seca, and “ecological refuges”).

Insights into the regulation of GPEET procyclin during differentiation from early to late procyclic forms of Trypanosoma brucei.

The procyclic form of Trypanosoma brucei colonises the gut of its insect vector, the tsetse fly. GPEET and EP procyclins constitute the parasite's surface coat at this stage of the life cycle, and the presence or absence of GPEET distinguishes between early and late procyclic forms, respectively. Differentiation from early to late procyclic forms in vivo occurs in the fly midgut and can be mimicked in culture. Our analysis of this transition in vitro delivered new insights into the process of GPEET repression. First, we could show that parasites followed a concrete sequence of events upon triggering differentiation: after undergoing an initial growth arrest, cells lost GPEET protein, and finally late procyclic forms resumed proliferation. Second, we determined the stability of both GPEET and EP mRNA during differentiation. GPEET mRNA is exceptionally stable in early procyclic forms, with a half-life >6h. The GPEET mRNA detected in late procyclic form cultures is a mixture of transcripts from both bona fide late procyclic forms and GPEET-positive 'laggard' parasites present in these cultures. However, its stability was clearly reduced during differentiation and in late procyclic form cultures. Alternatively processed GPEET transcripts were enriched in samples from late procyclic forms, suggesting that altered mRNA processing might contribute to repression of GPEET in this developmental stage. In addition, we detected GPEET transcripts with non-templated oligo(U) tails that were enriched in late procyclic forms. To the best of our knowledge, this is the first study reporting a uridylyl-tailed, nuclear-encoded mRNA species in trypanosomatids or any other protozoa.

Do binucleate cardiomyocytes have a role in myocardial repair? Insights using isolated rodent myocytes and cell culture.

Neonatal and adult cardiomyocytes were isolated from rat hearts. Some of the adult myocytes were cultured to allow for cell dedifferentiation, a phenomenon thought to mimic cell changes that occur in stressed myocardium, with myocytes regressing to a fetal pattern of metabolism and stellate neonatal shape.Using fluorescence deconvolution microscopy, cells were probed with fluorescent markers and scanned for a number of proteins associated with ion control, calcium movements and cardiac function. Image analysis of deconvoluted image stacks and sequential real-time image recordings of calcium transients of cells were made.All three myocyte groups were predominantly comprised of binucleate cells. Clustering of proteins to a single nucleus was a common observation, suggesting that one nucleus is active in protein synthesis pathways, while the other nucleus assumes a 'dormant' or different role and that cardiomyocytes might be mitotically active even in late development, or specific protein syntheses could be targeted and regulated for reintroduction into the cell cycle.Such possibilities would extend cardiac disease associated stem cell research and therapy options, while producing valuable insights into developmental and death pathways of binucleate cardiomyocytes (word count 183).

Rescue from apoptosis in early (CD34 selected) versus late (CD34 unselected) human hematopoietic cells by VLA-4 and VCAM-1 dependent adhesion to bone marrow stromal cells

The interaction of hematopoietic precursor cell with bone marrow stromal cells is assumed to be important to the survival of hematopoietic precursor cells during hematopoietic cell long-term culture. Early hematopoietic stem cells are preferentially found within the stromal adherent cell fraction in primary long-term bone marrow cultures. The purpose of this dissertation was to understand the molecular mechanisms that govern these interactions for the regulation of survival and proliferation of early versus late hematopoietic cells.^ Monoclonal antibodies to the VLA-4 recognize the alpha4 beta1 integrin receptor on human hematopoietic cells. This monoclonal antibody blocks the adhesion between early hematopoietic progenitor cells (CD34 selected cells) and stromal cells when added to cultures of these cells. Addition of the VLA-4 monoclonal antibody to cultures of stromal cells and CD34 selected cells was shown to induce apoptosis of CD34 selected cells in these CD34 selected cell/stromal cell cocultures, as measured by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling method. In contrast to these experiments with early hematopoietic progenitor cells (CD34+), the level of adhesion between more differentiated cells (unfractionated hematopoietic cells) and stromal cells was not significantly altered by addition of the anti-VLA-4 monoclonal antibody. Similarly, the level of apoptosis of unfractionated hematopoietic cells was not significantly increased by the addition of anti-VLA-4 monoclonal antibody to cultures of the latter cells with stromal cells. The binding of the unfractionated cells is less than that of the CD34 selected. Since there is no difference between the alpha4 beta1 integrin expression level of the early and late myeloid cells, there may be a difference in the functional state of the integrin between the early and late myeloid cells. We also show that CD34+ selected precursor cells proliferate at a higher rate when these cells are plated on recombinant VCAM-1 molecules. These data indicate that the alpha4beta1 integrin receptor (VLA-4) plays a central role in the apoptosis rescue function which results from the anchorage-dependent growth of the CD34 selected early hematopoietic cells on stromal cells. The data suggest that these apoptosis rescue pathways have less significance as the cells mature and become anchorage-independent in their growth. These data should assist in the design of systems for the ex vivo proliferation and transduction of early hematopoietic cells for genetic therapy. ^

The International Law of Culture : Prospects and Challenges

This is a conference review of an event on the international law of culture, which took place in late May 2012 at the University of Göttingen, Germany. The review provides context to it considering the complex landscape of international initiatives of hard and soft law nature, which address culture and their impact on the environment, where cultural rights are to be exercised.

Co-culture of Notochordal Cells with Nucleus pulposus and Annulus fibrosus cells under normoxia and hypoxia

Introduction Notochordal cells (NC) are shifted back into focus due to their apparent action of activating other disc cells via indirect release of yet unknown factors into the medium (conditioned medium = CM).1,2 Recent evidence confirms the results from the late 1990s.3,4 Here, we test porcine (p) NC cultured in 3D and the influence of adding serum or using serum-free medium onto the culture on NC cells and its stimulating effects for subsequent coculture with primary bovine (b) nucleus pulposus (bNPC) and annulus fibrous cells (bAFC). Materials and Methods Primary pNC, bNPC, and bAFC were isolated from porcine tails (< 6-12 months age) or bovine tails (∼1 year age), which were obtained from the food chain (N = 4 repeats) within 4 hours postmortem. All cells were seeded into 1.2% alginate, each with a density of 4 × 106/mL. NC were then either cultured for 7 days in serum free medium (SFM = Dulbecco modified eagle medium [DMEM] supplied with ITS+, 50 µg/mL vitamin C and nonessential amino acids) or DMEM + 10% fetal calf serum (FCS). CM was produced from NC collecting 4 mL SFM and keeping approximately 30 beads for 7 days. Then, a coculture was set up in SFM for 14 days using indirect cell-cell contact (culture insert, high density pore, 0.4 µm) using a 50:50% ratio5 of pNC:bNP or bAF, or by addition of CM, respectively. The cell activity, glycosaminoglycan per DNA (GAG/DNA) ratio, and real-time RT-PCR of IVD relevant genes were monitored. Mass spectrometry was performed on the SFM and the cocultured medium as well as the CM of the pNC to identify possible key cytokines to the stimulatory effects. Results The results for cell activity confirmed that pNC are highly responsive on the nutritional condition in the culture (K-W test, p = 0.048) after 7 days of coculture. bNPC and bAFC did not respond significantly different to coculture or addition of CM with respect to cell activity. However, GAG/DNA ratio of pNC was significantly upregulated if they were initially pre-exposed to FCS and in coculture with bNPC after 14 days, for both normoxia and hypoxia (K-W, p = 0.03). The bNPC were stimulated by both, 1:1 coculture with pNC but also by addition of CM only, which resulted in approximately 200% increased GAG/DNA values relative to the day 0 state. However, this doubling of the GAG/DNA ratio was nonsignificant after 14 days. The aggrecan/collagen type 2 ratio as quantified from real-time RT-PCR pointed to a beneficial state of the bNPC if cultured either in indirect coculture with pNC or by the addition of CM (Fig. 1). The mass spectrometric analysis of the CM revealed that there was connecting tissue growth factor present (CTGF) among the cytokine CLC11, a cytokine that has been found to be expressed in skeletal tissues including bone marrow and chondrocytes among other factors that might have immunoregulatory and cell proliferative functions.

Magnetic properties of two cores from the Iberian Margin

Magnetic properties of late Quaternary sediments on the SW Iberian Margin are dominated by bacterial magnetite, observed by transmission electron microscopy (TEM), with contributions from detrital titanomagnetite and hematite. Reactive hematite from eolian dust, together with low organic matter concentrations and the lack of sulfate reduction, lead to dissimilatory iron reduction and availability of Fe(II) for abundant magnetotactic bacteria. Magnetite grain-size proxies (kARM/k and ARM/IRM) and S-ratios (sensitive to hematite) vary on stadial/interstadial timescales, contain orbital power, and mimic planktic d18O. The detrital/biogenic magnetite ratio and hematite concentration are greater during stadials and glacial isotopic stages, reflecting increased detrital (magnetite) input during times of lowered sea level, coinciding with atmospheric conditions favoring hematitic dust supply. Magnetic susceptibility, on the other hand, has a very different response being sensitive to coarse detrital multidomain (MD) magnetite associated with ice-rafted debris (IRD). High susceptibility and/or magnetic grain size coarsening, mark Heinrich stadials (HS), particularly HS2, HS3, HS4, HS5, HS6 and HS7, as well as older Heinrich-like detrital layers, indicating the sensitivity of this region to fluctuations in the position of the polar front. Relative paleointensity (RPI) records have well-constrained age models based on planktic d18O correlation to ice-core chronologies, however, they differ from reference records (e.g. PISO) particularly in the vicinity of glacial maxima, mainly due to inefficient normalization of RPI records in intervals of enhanced detrital/eolian hematite input.

Alkenones and coccolithophorids in late Quaternary sediments from the Walvis Ridge

Sea surface temperatures (SSTs) derived from the alkenone UK'37) record of Quaternary sediments may be subject to bias if algae with different temperature sensitivities have contributed to the sedimentary alkenone record. The alkenone-derived SST records are usually based on a UK'37-temperature relationship which was measured in culture experiments using the coccolithophorid Emiliania huxleyi (F.G. Prahl, L.A. Muehlhausen and D.L. Zahnle, 1988. Further evaluation of long-chain alkenones as indicators of paleoceanographic conditions. Geochim. Cosmochim. Acta 52, 2303-2310). To assess possible effects of past species changes on the UK'37-temperature signal, we have analyzed long-chain alkenones and coccolithophorids in a late Quaternary sediment core from the Walvis Ridge and compared the results to SST estimates extracted from the d18O record of the planktonic foraminifer Globigerinoides ruber. Alkenones and isotopes were determined over the entire 400-kyr core record while the coccolithophorid study was confined to the last 200 kyr when the most pronounced changes in alkenone content occurred. Throughout oxygen-isotope stages 6 and 5, species of the genus Gephyrocapsa were the predominating coccolithophorids. E. huxleyi began to increase systematically in relative abundance since the stage 5/4 transition, became dominant over Gephyrocapsa spp. during stage 3 and reached the highest abundances in the Holocene. Carbon-normalized alkenone concentrations are inversely related to the relative abundances of E. huxleyi, and directly related to that of Gephyrocapsa spp., suggesting that species of this genus were the principal alkenone contributors to the sediments. Nevertheless, SST values obtained from the UK'37-temperature relationship for E. huxleyi compare favourably to the isotope-derived temperatures. The recently reported UK'37-temperature relationship for a single strain of Gephyrocapsa oceanica (J.K. Volkman. S.M. Barrett, S.I. Blackburn and E.L. Sikes, 1995. Alkenones in Gephyrocapsa oceanica: Implications for studies of paleoclimate. Geochim. Cosmochim. Acta 59, 513-520) produces unrealistically high SST values indicating that the temperature response of the examined strain is not typical for the genus Gephyrocapsa. This is supported by the C37:C38, alkenone ratios of the sediments which are comparable to average ratios reported for E. huxleyi, but significantly higher than for the G. oceanica strain. Most notably, the general accordance of the alkenone characteristics between sediments and E. huxleyi persists through stages 8 to 5 and even in times that predate the first appearance of this species (268 ka; H.R. Thierstein, K.R. Geitzenauer and B. Molfino, 1977. Global synchroneity of late Quaternary coccolith datum levels: Validation by oxygen isotopes. Geology 5, 400-404). Our results suggest that UK'37-temperature relationships based on E. huxleyi produce reasonable paleo-SST estimates even for late Quaternary periods when this species was scarce or absent because other alkenone-synthesizing algae, e.g. of the genus Gephyrocapsa.

Late Gothic German Vault Design Methods and Its Relationship with Spanish Ribbed Vaults

The arrival of European master masons to Burgos and Toledo during the mid-fifteenth century was essential for the promotion of the late Gothic ribbed vault design techniques in Spain. The Antigua Chapel in Seville Cathedral, designed by the Spanish master mason Simón de Colonia on 1497, provides an outstanding case study on this subject. This vault is characterized by the interlacing of the ribs near the springing, reflecting the influence of German ribbed vault designs. This paper analyses the relationship between German ribbed vaults and their design methods with those of Spanish ribbed vaults; with particular attention to the presence of ribs that cut through one another above the springing, materialized in the work of Simón de Colonia. This characteristic is reflected in some manuscripts in the German area, like the Wiener Sammlungen (15th-16th centuries) and the Codex Miniatus 3 (ca. 1560-1570), but no Spanish documents of the same period make reference to it.

The late Miocene macroflora of the La Cerdaña Basin, Eastern Pirenees, Spain. Towards a Synthesis

The fossil plant-bearing beds of the Tortonian (late Miocene) intramontane basin of La Cerdanya (Eastern Pyrenees, Catalonia, Spain) have been investigated for more than a century, and 165 species from 12 outcrops have been described in previous publications. The sediments with rich plant fossil assemblages, which correspond to lacustrine diatomitic deposits, contain large numbers of plant remains, mainly leaf compressions and impressions. These assemblages are well preserved, a consequence of the rapid accumulation of plant remains in the sediments of the basin's ancient lake, and the often close proximity of its shores to wetland and upland vegetation. This paper provides a comprehensive taxonomic and nomenclatural review of the historic and new collections of late Miocene macroflora for the La Cerdanya Basin. Examination of the newer materials allowed emendments to be made to the diagnoses ofAbies saportana, Acer pyrenakum,Alnus occidentalis, Quercus hispanka and Tilia vidali provided by REROLLE for the basin at the end of the 19th century. In addition, 24 species of vascular plants are identified for the basin for the first time, including one horsetail, three conifers, 19 arboreal or bushy dicotyledonous angiosperms, and one monocotyledonous angiosperm. Indeed, this is the first time that Cedrela helkonia (UNGER) KNOBLOCH, Decodon sp„ Hedera cf multinervis KOLAKOVSKII, Mahonia cf pseudosimplex KVACEK & WALTHER, Smilax cf. aspera L. vm.fossilis and Ulmus cf. plurinervia UNGER have been recorded anywhere in the Iberian Peninsula. The La Cerdanya Basin plant assemblages of the late Miocene mainly consisted of conifers and deciduous broadleaved taxa of Arctotertiary origin; evergreen Palaeotropical elements were less well represented. This flora is similar to those recorded at coeval sites in northern Greece, northern Italy and central and eastern France. Within the Iberian Peninsula, the late Miocene macroflora reported for the nearby Seu d'Urgell Basin is the most similar.

More macrofossils are needed to successfully model late-quaternary vegetation

The need of more macrofossils to model late-quaternary vegetation is emphasized in the light of Iberian palaeobotanical data